Protection to immune system of mice by N-acetyl tryptophan glucoside (NATG) against gamma radiation induced immune suppression

Poonam Malhotra; Ashutosh K Gupta; Darshana Singh; Saurabh Mishra; Shravan K Singh; Raj Kumar

doi:10.1016/j.molimm.2019.09.003

Protection to immune system of mice by N-acetyl tryptophan glucoside (NATG) against gamma radiation induced immune suppression

Mol Immunol. 2019 Oct:114:578-590. doi: 10.1016/j.molimm.2019.09.003. Epub 2019 Sep 14.

Authors

Poonam Malhotra¹, Ashutosh K Gupta¹, Darshana Singh¹, Saurabh Mishra¹, Shravan K Singh¹, Raj Kumar²

Affiliations

¹ Department of Radiation Biotechnology, Division of Radioprotective Drug Development and Research, Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, India.
² Department of Radiation Biotechnology, Division of Radioprotective Drug Development and Research, Institute of Nuclear Medicine and Allied Sciences, DRDO, Delhi, India. Electronic address: rajkumar@inmas.drdo.in.

PMID: 31526941
DOI: 10.1016/j.molimm.2019.09.003

Abstract

Immune system is a critical modulator of radiation-induced biological effects. In this study, we have assessed protective potential of N-acetyl tryptophan glucoside (NATG) pre-treatment in bone marrow of gamma radiation challenged mice. Isolated bone marrow cells were analysed for cell cycle progression by flow cytometry, while various pro-/anti-inflammatory cytokine profiles were performed by ELISA method. Overall radioprotective ability of NATG in ensuring protection against gamma radiation-induced damage was assessed by evaluating whole body survival analysis and haematological studies on 9 Gy irradiated mice with/without NATG pre-treatment. Results exhibited pre-treatment with 150 mg/kg b.wt oral administration of NATG as most effective against 9 Gy radiation exposure. Moreover, NATG showed non-interfering effect on cell cycle progression in pre-treated irradiated mice group when compared to radiation alone group. In addition, cytokine expression analysis indicated significant (p > 0.05) elevation in levels of IFN-γ, IL-2, IL-12, IL-13 and IL-17 in NATG pre-treated irradiated mice in comparison to radiation alone group. On the contrary, NATG pre-treatment was observed to alleviate levels of TNF-α and IL-10 significantly (p < 0.05) in radiated group as compared to only irradiated mice group. Furthermore, NATG pre-treatment to 9 Gy radiation exposed mice aided in restoring their haematological parameters in terms of haemoglobin counts, RBC counts, WBC counts, hematocrit levels, platelets and granulocyte levels in comparison to irradiated alone mice, thus enhancing their immune system and contributing towards a better survival against gamma radiation-induced deleterious effects. Conclusively, this study highlights the potential of NATG as a prospective radiation countermeasure agent against ionizing radiation-induced assaults to the immune system.

Keywords: Bacterial secondary metabolite; Cell cycle analysis; Haematological studies; Haematopoiesis; Immunosuppression; Radioprotection.

Publication types

Research Support, Non-U.S. Gov't

MeSH terms

Animals
Apoptosis / drug effects
Cytokines / metabolism
Gamma Rays / adverse effects*
Immunosuppression Therapy / adverse effects*
Interleukin-10 / metabolism
Interleukin-13 / metabolism
Interleukin-17 / metabolism
Macrophages / drug effects
Macrophages / metabolism
Male
Mice
Protective Agents / pharmacology*
Tryptophan / analogs & derivatives
Tryptophan / pharmacology
Tumor Necrosis Factor-alpha / metabolism

Substances

Cytokines
Interleukin-13
Interleukin-17
N-acetyl tryptophan-glucopyranoside
Protective Agents
Tumor Necrosis Factor-alpha
Interleukin-10
Tryptophan